Classical and nonclassical effects of angiotensin-converting enzyme: How increased ACE enhances myeloid immune function.

As part of the classical renin-angiotensin system, the peptidase angiotensin-converting enzyme (ACE) makes angiotensin II which has myriad effects on systemic cardiovascular function, inflammation, and cellular proliferation. Less well known is that macrophages and neutrophils make ACE in response to immune activation which has marked effects on myeloid cell function independent of angiotensin II. Here, we discuss both classical (angiotensin) and nonclassical functions of ACE and highlight mice called ACE 10/10 in which genetic manipulation increases ACE expression by macrophages and makes these mice much more resistant to models of tumors, infection, atherosclerosis, and Alzheimer's disease. In another model called NeuACE mice, neutrophils make increased ACE and these mice are much more resistant to infection. In contrast, ACE inhibitors reduce neutrophil killing of bacteria in mice and humans. Increased expression of ACE induces a marked increase in macrophage oxidative metabolism, particularly mitochondrial oxidation of lipids, secondary to increased peroxisome proliferator-activated receptor α expression, and results in increased myeloid cell ATP. ACE present in sperm has a similar metabolic effect, and the lack of ACE activity in these cells reduces both sperm motility and fertilization capacity. These nonclassical effects of ACE are not due to the actions of angiotensin II but to an unknown molecule, probably a peptide, that triggers a profound change in myeloid cell metabolism and function. Purifying and characterizing this peptide could offer a new treatment for several diseases and prove potentially lucrative.

Testicular ACE regulates sperm metabolism and fertilization through the transcription factor PPARγ.

Testis angiotensin-converting enzyme (tACE) plays a critical role in male fertility, but the mechanism is unknown. By using ACE C-domain KO (CKO) mice which lack tACE activity, we found that ATP in CKO sperm was 9.4-fold lower than WT sperm. Similarly, an ACE inhibitor (ACEi) reduced ATP production in mouse sperm by 72%. Metabolic profiling showed that tACE inactivation severely affects oxidative metabolism with decreases in several Krebs cycle intermediates including citric acid, cis-aconitic acid, NAD, α-ketoglutaric acid, succinate, and L-malic acid. We found that sperms lacking tACE activity displayed lower levels of oxidative enzymes (CISY, ODO1, MDHM, QCR2, SDHA, FUMH, CPT2, and ATPA) leading to a decreased mitochondrial respiration rate. The reduced energy production in CKO sperms leads to defects in their physiological functions including motility, acrosine activity, and fertilization in vitro and in vivo. Male mice treated with ACEi show severe impairment in reproductive capacity when mated with female mice. In contrast, an angiotensin II receptor blocker (ARB) had no effect. CKO sperms express significantly less peroxisome proliferators-activated receptor gamma (PPARγ) transcription factor, and its blockade eliminates the functional differences between CKO and WT sperms, indicating PPARγ might mediate the effects of tACE on sperm metabolism. Finally, in a cohort of human volunteers, in vitro treatment with the ramipril or a PPARγ inhibitor reduced ATP production in human sperm and hence its motility and acrosine activity. These findings may have clinical significance since millions of people take ACEi daily, including men who are reproductively active.

Diverse biological functions of the renin-angiotensin system.

The renin-angiotensin system (RAS) has been widely known as a circulating endocrine system involved in the control of blood pressure. However, components of RAS have been found to be localized in rather unexpected sites in the body including the kidneys, brain, bone marrow, immune cells, and reproductive system. These discoveries have led to steady, growing evidence of the existence of independent tissue RAS specific to several parts of the body. It is important to understand how RAS regulates these systems for a variety of reasons: It gives a better overall picture of human physiology, helps to understand and mitigate the unintended consequences of RAS-inhibiting or activating drugs, and sets the stage for potential new therapies for a variety of ailments. This review fulfills the need for an updated overview of knowledge about local tissue RAS in several bodily systems, including their components, functions, and medical implications.

Epidermal growth factor receptor activation confers resistance to lenvatinib in thyroid cancer cells.

Thyroid cancer is the most common endocrine malignancy. A multitargeted tyrosine kinase inhibitor, lenvatinib, has been used for the treatment of advanced thyroid cancer. To elucidate the mechanism of resistance to lenvatinib in thyroid cancer cells, we established lenvatinib-resistant sublines and analyzed the molecular mechanisms of resistance. Two thyroid cancer cell lines (TPC-1 and FRO) were used, and resistant sublines for lenvatinib (TPC-1/LR, FRO/LR) were established. In TPC-1/LR, the phosphorylation of epidermal growth factor receptor (EGFR), extracellular signal-regulated kinase (ERK), and Akt was enhanced whereas in FRO/LR, the phosphorylation of EGFR and downstream signal transduction molecules was not enhanced. The addition of epidermal growth factor decreased sensitivity to lenvatinib in TPC-1 and FRO. The combination of EGFR inhibitors lapatinib and lenvatinib significantly inhibited the growth of TPC-1/LR in both in vitro and mouse xenograft models. Short-term exposure to lenvatinib enhanced the phosphorylation of EGFR in six thyroid cancer cell lines regardless of their histological origin or driver gene mutations; however, phosphorylation of ERK was enhanced in all cells except TPC-1. A synergistic growth-inhibitory effect was observed in three thyroid cancer cell lines, including intrinsically lenvatinib-resistant cells. The results indicate that signal transduction via the EGFR pathway may be involved in the development of lenvatinib resistance in thyroid cancer cells. The inhibition of the EGFR pathway simultaneously by an EGFR inhibitor may have therapeutic potential for overcoming lenvatinib resistance in thyroid cancer.

Selective and reversible modification of kinase cysteines with chlorofluoroacetamides.

Irreversible inhibition of disease-associated proteins with small molecules is a powerful approach for achieving increased and sustained pharmacological potency. Here, we introduce α-chlorofluoroacetamide (CFA) as a novel warhead of targeted covalent inhibitor (TCI). Despite weak intrinsic reactivity, CFA-appended quinazoline showed high reactivity toward Cys797 of epidermal growth factor receptor (EGFR). In cells, CFA-quinazoline showed higher target specificity for EGFR than the corresponding Michael acceptors in a wide concentration range (0.1-10 µM). The cysteine adduct of the CFA derivative was susceptible to hydrolysis and reversibly yielded intact thiol but was stable in solvent-sequestered ATP-binding pocket of EGFR. This environment-dependent hydrolysis can potentially reduce off-target protein modification by CFA-based drugs. Oral administration of CFA quinazoline NS-062 significantly suppressed tumor growth in a mouse xenograft model. Further, CFA-appended pyrazolopyrimidine irreversibly inhibited Bruton's tyrosine kinase with higher target specificity. These results demonstrate the utility of CFA as a new class warheads for TCI.

Blue as an Underrated Alternative to Green: Photoplethysmographic Heartbeat Intervals Estimation under Two Temperature Conditions.

Since photoplethysmography (PPG) sensors are usually placed on open skin areas, temperature interference can be an issue. Currently, green light is the most widely used in the reflectance PPG for its relatively low artifact susceptibility. However, it has been known that hemoglobin absorption peaks at the blue part of the spectrum. Despite this fact, blue light has received little attention in the PPG field. Blue wavelengths are commonly used in phototherapy. Combining blue light-based treatments with simultaneous blue PPG acquisition could be potentially used in patients monitoring and studying the biological effects of light. Previous studies examining the PPG in blue light compared to other wavelengths employed photodetectors with inherently lower sensitivity to blue, thereby biasing the results. The present study assessed the accuracy of heartbeat intervals (HBIs) estimation from blue and green PPG signals, acquired under baseline and cold temperature conditions. Our PPG system is based on TCS3472 Color Sensor with equal sensitivity to both parts of the light spectrum to ensure unbiased comparison. The accuracy of the HBIs estimates, calculated with five characteristic points (PPG systolic peak, maximum of the first PPG derivative, maximum of the second PPG derivative, minimum of the second PPG derivative, and intersecting tangents) on both PPG signal types, was evaluated based on the electrocardiographic values. The statistical analyses demonstrated that in all cases, the HBIs estimation accuracy of blue PPG was nearly equivalent to the G PPG irrespective of the characteristic point and measurement condition. Therefore, blue PPG can be used for cardiovascular parameter acquisition. This paper is an extension of work originally presented at the 42nd Annual International Conference of the IEEE Engineering in Medicine and Biology Society.

Oncogenic Y-box binding protein-1 as an effective therapeutic target in drug-resistant cancer.

Y-box binding protein-1 (YBX1), a multifunctional oncoprotein containing an evolutionarily conserved cold shock domain, dysregulates a wide range of genes involved in cell proliferation and survival, drug resistance, and chromatin destabilization by cancer. Expression of a multidrug resistance-associated ATP binding cassette transporter gene, ABCB1, as well as growth factor receptor genes, EGFR and HER2/ErbB2, was initially discovered to be transcriptionally activated by YBX1 in cancer cells. Expression of other drug resistance-related genes, MVP/LRP, TOP2A, CD44, CD49f, BCL2, MYC, and androgen receptor (AR), is also transcriptionally activated by YBX1, consistently indicating that YBX1 is involved in tumor drug resistance. Furthermore, there is strong evidence to support that nuclear localization and/or overexpression of YBX1 can predict poor outcomes in patients with more than 20 different tumor types. YBX1 is phosphorylated by kinases, including AKT, p70S6K, and p90RSK, and translocated into the nucleus to promote the transcription of resistance- and malignancy-related genes. Phosphorylated YBX1, therefore, plays a crucial role as a potent transcription factor in cancer. Herein, a novel anticancer therapeutic strategy is presented by targeting activated YBX1 to overcome drug resistance and malignant progression.

Oxidation Induced Doping of Nanoparticles Revealed by in Situ X-ray Absorption Studies.

Doping is a well-known approach to modulate the electronic and optical properties of nanoparticles (NPs). However, doping at nanoscale is still very challenging, and the reasons for that are not well understood. We studied the formation and doping process of iron and iron oxide NPs in real time by in situ synchrotron X-ray absorption spectroscopy. Our study revealed that the mass flow of the iron triggered by oxidation is responsible for the internalization of the dopant (molybdenum) adsorbed at the surface of the host iron NPs. The oxidation induced doping allows controlling the doping levels by varying the amount of dopant precursor. Our in situ studies also revealed that the dopant precursor substantially changes the reaction kinetics of formation of iron and iron oxide NPs. Thus, in the presence of dopant precursor we observed significantly faster decomposition rate of iron precursors and substantially higher stability of iron NPs against oxidation. The same doping mechanism and higher stability of host metal NPs against oxidation was observed for cobalt-based systems. Since the internalization of the adsorbed dopant at the surface of the host NPs is driven by the mass transport of the host, this mechanism can be potentially applied to introduce dopants into different oxidized forms of metal and metal alloy NPs providing the extra degree of compositional control in material design.

Heterogeneous nucleation and shape transformation of multicomponent metallic nanostructures.

To be able to control the functions of engineered multicomponent nanomaterials, a detailed understanding of heterogeneous nucleation at the nanoscale is essential. Here, by using in situ synchrotron X-ray scattering, we show that in the heterogeneous nucleation and growth of Au on Pt or Pt-alloy seeds the heteroepitaxial growth of the Au shell exerts high stress (∼2 GPa) on the seed by forming a core/shell structure in the early stage of the reaction. The development of lattice strain and subsequent strain relaxation, which we show using atomic-resolution transmission electron microscopy to occur through the slip of {111} layers, induces morphological changes from a core/shell to a dumbbell structure, and governs the nucleation and growth kinetics. We also propose a thermodynamic model for the nucleation and growth of dumbbell metallic heteronanostructures.

Local structure, composition, and crystallization mechanism of a model two-phase "composite nanoglass".

We report a detailed study of the local composition and structure of a model, bi-phasic nanoglass with nominal stoichiometry Cu55Nb45. Three dimensional atom probe data suggest a nanoscale-phase-separated glassy structure having well defined Cu-rich and Nb-rich regions with a characteristic length scale of ≈ 3 nm. However, extended x-ray absorption fine structure analysis indicates subtle differences in the local environments of Cu and Nb. While the Cu atoms displayed a strong tendency to cluster and negligible structural order beyond the first coordination shell, the Nb atoms had a larger fraction of unlike neighbors (higher chemical order) and a distinctly better-ordered structural environment (higher topological order). This provides the first experimental indication that metallic glass formation may occur due to frustration arising from the competition between chemical ordering and clustering. These observations are complemented by classical as well as ab initio molecular dynamics simulations. Our study indicates that these nanoscale phase-separated glasses are quite distinct from the single phase nanoglasses (studied by Gleiter and others) in the following three respects: (i) they contain at least two structurally and compositionally distinct, nanodispersed, glassy phases, (ii) these phases are separated by comparatively sharp inter-phase boundaries, and (iii) thermally induced crystallization occurs via a complex, multi-step mechanism. Such materials, therefore, appear to constitute a new class of disordered systems that may be called a composite nanoglass.

Discharge-rate persistence of baseline activity during fixation reflects maintenance of memory-period activity in the macaque posterior parietal cortex.

Recent evidence has demonstrated that spatiotemporal patterns of spontaneous activity reflect the patterns of activity evoked by sensory stimuli. However, few studies have examined whether response profiles of task-evoked activity, which is not related to external sensory stimuli but rather to internal processes, are also reflected in those of spontaneous activity. To address this, we recorded activity of neurons in the lateral intraparietal area (LIP) when monkeys performed reaction-time and delayed-response visual-search tasks. We particularly focused on the target location-dependent modulation of delay-period activity (delay-period modulation) in the delayed-response task, and the discharge-rate persistency in fixation-period activity (baseline-activity maintenance) in the reaction-time task. Baseline-activity maintenance was assessed by the correlation between the spike counts of 2 separate bins. We found that baseline-activity maintenance, calculated from bins separated by a long interval (200-500 ms), was correlated with delay-period modulation, whereas that calculated from bins separated by a short interval (~100 ms) was correlated with trial-to-trial fluctuations in baseline activity, suggesting a link between the capability to hold task-related information in delay-period activity and the degree of baseline-activity maintenance in a timescale-dependent manner.

N-myc downstream-regulated gene 1 promotes tumor inflammatory angiogenesis through JNK activation and autocrine loop of interleukin-1α by human gastric cancer cells.

The expression of N-myc downstream-regulated gene 1 (NDRG1) was significantly correlated with tumor angiogenesis and malignant progression together with poor prognosis in gastric cancer. However, the underlying mechanism for the role of NDRG1 in the malignant progression of gastric cancer remains unknown. Here we examined whether and how NDRG1 could modulate tumor angiogenesis by human gastric cancer cells. We established NU/Cap12 and NU/Cap32 cells overexpressing NDRG1 in NUGC-3 cells, which show lower tumor angiogenesis in vivo. Compared with parental NU/Mock3, NU/Cap12, and NU/Cap32 cells: 1) induced higher tumor angiogenesis than NU/Mock3 cells accompanied by infiltration of tumor-associated macrophages in mouse dorsal air sac assay and Matrigel plug assay; 2) showed much higher expression of CXC chemokines, MMP-1, and the potent angiogenic factor VEGF-A; 3) increased the expression of the representative inflammatory cytokine, IL-1α; 4) augmented JNK phosphorylation and nuclear expression of activator protein 1 (AP-1). Further analysis demonstrated that knockdown of AP-1 (Jun and/or Fos) resulted in down-regulation of the expression of VEGF-A, CXC chemokines, and MMP-1, and also suppressed expression of IL-1α in NDRG1-overexpressing cell lines. Treatment with IL-1 receptor antagonist (IL-1ra) resulted in down-regulation of JNK and c-Jun phosphorylation, and the expression of VEGF-A, CXC chemokines, and MMP-1 in NU/Cap12 and NU/Cap32 cells. Finally, administration of IL-1ra suppressed both tumor angiogenesis and infiltration of macrophages by NU/Cap12 in vivo. Together, activation of JNK/AP-1 thus seems to promote tumor angiogenesis in relationship to NDRG1-induced inflammatory stimuli by gastric cancer cells.

In situ optical and structural studies on photoluminesence quenching in CdSe/CdS/Au heterostructures.

We report here detailed in situ studies of nucleation and growth of Au on CdSe/CdS nanorods using synchrotron SAXS technique and time-resolved spectroscopy. We examine structural and optical properties of CdSe/CdS/Au heterostructures formed under UV illumination. We compare the results for CdSe/CdS/Au heterostructures with the results of control experiments on CdSe/CdS nanorods exposed to gold precursor under conditions when no such heterostructures are formed (no UV illumination). Our data indicate similar photoluminescence (PL) quenching and PL decay profiles in both types of samples. Via transient absorption and PL, we show that such behavior is consistent with rapid (faster than 3 ps) hole trapping by gold-sulfur sites at the surface of semiconductor nanoparticles. This dominant process was overlooked in previous end-point studies on semiconductor/metal heterostructures.

Continuous and simultaneous estimation of finger kinematics using inputs from an EMG-to-muscle activation model.

BACKGROUND: Surface electromyography (EMG) signals are often used in many robot and rehabilitation applications because these reflect motor intentions of users very well. However, very few studies have focused on the accurate and proportional control of the human hand using EMG signals. Many have focused on discrete gesture classification and some have encountered inherent problems such as electro-mechanical delays (EMD). Here, we present a new method for estimating simultaneous and multiple finger kinematics from multi-channel surface EMG signals. METHOD: In this study, surface EMG signals from the forearm and finger kinematic data were extracted from ten able-bodied subjects while they were tasked to do individual and simultaneous multiple finger flexion and extension movements in free space. Instead of using traditional time-domain features of EMG, an EMG-to-Muscle Activation model that parameterizes EMD was used and shown to give better estimation performance. A fast feed forward artificial neural network (ANN) and a nonparametric Gaussian Process (GP) regressor were both used and evaluated to estimate complex finger kinematics, with the latter rarely used in the other related literature. RESULTS: The estimation accuracies, in terms of mean correlation coefficient, were 0.85 ± 0.07, 0.78 ± 0.06 and 0.73 ± 0.04 for the metacarpophalangeal (MCP), proximal interphalangeal (PIP) and the distal interphalangeal (DIP) finger joint DOFs, respectively. The mean root-mean-square error in each individual DOF ranged from 5 to 15%. We show that estimation improved using the proposed muscle activation inputs compared to other features, and that using GP regression gave better estimation results when using fewer training samples. CONCLUSION: The proposed method provides a viable means of capturing the general trend of finger movements and shows a good way of estimating finger joint kinematics using a muscle activation model that parameterizes EMD. The results from this study demonstrates a potential control strategy based on EMG that can be applied for simultaneous and continuous control of multiple DOF(s) devices such as robotic hand/finger prostheses or exoskeletons.

Peroxisome proliferator-activated receptor alpha is essential factor in enhanced macrophage immune function induced by angiotensin converting enzyme.

An upregulation of angiotensin-converting enzyme (ACE) expression strengthens the immune activity of myeloid lineage cells as a natural functional regulation mechanism in our immunity. ACE10/10 mice, possessing increased ACE expression in macrophages, exhibit enhanced anti-tumor immunity and anti-bactericidal effects compared to those of wild type (WT) mice, while the detailed molecular mechanism has not been elucidated yet. In this report, we demonstrate that peroxisome proliferator-activated receptor alpha (PPARα) is a key molecule in the functional upregulation of macrophages induced by ACE. The expression of PPARα, a transcription factor regulating fatty acid metabolism-associated gene expressions, was upregulated in ACE-overexpressing macrophages. To pinpoint the role of PPARα in the enhanced immune function of ACE-overexpressing macrophages, we established a line with myeloid lineage-selective PPARα depletion employing the Lysozyme 2 (LysM)-Cre system based on ACE 10/10 mice (named A10-PPARα-Cre). Interestingly, A10-PPARα-Cre mice exhibited larger B16-F10-originated tumors than original ACE 10/10 mice. PPARα depletion impaired cytokine production and antigen-presenting activity in ACE-overexpressing macrophages, resulting in reduced tumor antigen-specific CD8+ T cell activity. Additionally, the anti-bactericidal effect was also impaired in A10-PPARα-Cre mice, resulting in similar bacterial colonization to WT mice in Methicillin-Resistant Staphylococcus aureus (MRSA) infection. PPARα depletion downregulated phagocytic activity and bacteria killing in ACE-overexpressing macrophages. Moreover, THP-1-ACE-derived macrophages, as a human model, expressing upregulated PPARα exhibited enhanced cytotoxicity against B16-F10 cells and MRSA killing. These activities were further enhanced by the PPARα agonist, WY 14643, while abolished by the antagonist, GW6471, in THP-1-ACE cells. Thus, PPARα is an indispensable molecule in ACE-dependent functional upregulation of macrophages in both mice and humans.

Comprehensive characterization of the structure of Zr-based metallic glasses.

Structure of metallic glasses fascinates as the generic amorphous structural template for ubiquitous systems. Its specification necessitates determination of the complete hierarchical structure, starting from short-range-order (SRO) → medium-range-order (MRO) → bulk structure and free volume (FV) distribution. This link has largely remained elusive since previous investigations adopted one-technique-at-a-time approach, focusing on limited aspects of any one domain. Reconstruction of structure from experimental data inversion is non-unique for many of these techniques. As a result, complete and precise structural understanding of glass has not emerged yet. In this work, we demonstrate the first experimental pathway for reconstruction of the integrated structure, for Zr 67 Ni 33 and Zr 52 Ti 6 Al 10 Cu 18 Ni 14 glasses. Our strategy engages diverse (× 7) multi-scale techniques [XAFS, 3D-APT, ABED/NBED, FEM, XRD, PAS, FHREM] on the same glass. This strategy complemented mutual limitations of techniques and corroborated common parameters to generate complete, self-consistent and precise parameters. Further, MRO domain size and inter-void separation were correlated to identify the presence of FV at MRO boundaries. This enabled the first experimental reconstruction of hierarchical subset: SRO → MRO → FV → bulk structure. The first ever image of intermediate region between MRO domains emerged from this link. We clarify that determination of all subsets is not our objective; the essence and novelty of this work lies in directing the pathway towards finite solution, in the most logical and unambiguous way.

Self-recognition of structurally identical, rod-shaped macroions with different central metal atoms during their assembly process.

Two rod-shaped macroanions, ((C4H9)4N)7[Mo6O18NC(OCH2)3XMo6O18(OCH2)3CNMo6O18] (X = Mn(III) (1), Fe(III) (2)), with almost identical charge densities and morphologies except for their different encapsulated central metal atoms were each observed to self-assemble into "blackberry"-type supramolecular structures in their dilute solution, driven by the counterion-mediated attraction. Amazingly, the two macroions remained self-sorted and self-assembled into homogeneous assemblies in their mixed solutions, demonstrating a self-recognition behavior between two highly similar macroions during their assembly process, as confirmed by DLS, SLS, and TEM/EDS analysis. This self-recognition behavior can be explained by the slightly different charge distributions of the macroanions resulting from their different central atoms (confirmed by theoretical DFT calculations and dissociation experiments) and the high activation energy of the slow assembly process, which suppresses the formation of hybrid oligomers at the beginning of the self-assembly process. This work confirms that the long-range counterion-mediated electrostatic attraction is sensitive to the small difference in macroions and consequently offers the possibility for delicate selectivity and preference among different macroions. This phenomenon might be directly related to (and be the important reason for) some recognition behaviors in biological systems.

[Complications in posterior segment after transscleral suturing of the posterior chamber in intraocular lens implantation].

PURPOSE: To investigate complications in the posterior segment after transscleral suturing of the posterior chamber in intraocular lens (PC-IOL) implantation. METHODS: Preoperative clinical characteristics and clinical course were analyzed in 13 eyes of 13 patients who underwent vitreous surgery for either suprachoroidal hemorrhage or rhegmatogenous retinal detachment after transscleral suturing in PC-IOL implantation. RESULTS: Preoperative low intraocular pressure (IOP) was found in 3 of 6 eyes with suprachoroidal hemorrhage (50%) and longer axial length in 3 eyes (50%). Retinal reattachment was achieved in 4 eyes (67%) and final vision was more than 0.1 in 3 eyes (50%). In 7 eyes of retinal detachment, retinal tear was undetected preoperatively in 3 eyes (43%), and retinal breaks were located in the superior quadrant in 5 eyes (71%), similar to the characteristics of aphakic retinal detachment. The retina was reattached in all eyes and vision improved to more than 2 Snellen lines in 6 eyes(86%). CONCLUSION: Low IOP caused by leakage from the scleral wound was a potential risk for developing suprachoroidal hemorrhage after transscleral suturing in PC-IOL implantation. A complete closure of the wounds may prevent suprachoroidal hemorrhage. Collapse and incarceration of the peripheral vitreous may cause retinal detachment and complete removal of the peripheral vitreous may prevent retinal detachment.

Multi-view image-based behavior classification of wet-dog shake in Kainate rat model.

The wet-dog shake behavior (WDS) is a short-duration behavior relevant to the study of various animal disease models, including acute seizures, morphine abstinence, and nicotine withdrawal. However, no animal behavior detection system has included WDS. In this work, we present a multi-view animal behavior detection system based on image classification and use it to detect rats' WDS behavior. Our system uses a novel time-multi-view fusion scheme that does not rely on artificial features (feature engineering) and is flexible to adapt to other animals and behaviors. It can use one or more views for higher accuracy. We tested our framework to classify WDS behavior in rats and compared the results using different amounts of cameras. Our results show that the use of additional views increases the performance of WDS behavioral classification. With three cameras, we achieved a precision of 0.91 and a recall of 0.86. Our multi-view animal behavior detection system represents the first system capable of detecting WDS and has potential applications in various animal disease models.

Corrigendum: Estimation of subjective quality of life in schizophrenic patients using speech features.

[This corrects the article DOI: 10.3389/fresc.2023.1121034.].